产品描述:
LY2090314 is potent and selective inhibitor of glycogen synthase kinase 3 (GSK3) with IC50 values of 1.5 and 0.9 nM for human recombinant GSK3α and GSK3β, respectively.{39184} It has >10-fold selectivity for GSK3 over a panel of 40 kinases at a concentration of 20 μM. LY2090314 induces time-dependent stabilization of β-catenin total protein and activates Wnt signaling in vitro. It has potent antiproliferative activity in BRAF wild-type/NRAS mutant and BRAF mutant melanoma cell lines (IC50s = 6.0-11.8 nM) but has limited to no activity in non-melanoma cell lines with (IC50s = 430 to >20,000 nM). Knockdown of β-catenin in A375 and M14 melanoma cells induces LY2090314 resistance in vitro, indicating that LY2090314-induced cell death is dependent upon Wnt activation. In vivo, LY2090314 reduces tumor volume in a murine A375 melanoma xenograft model as a single agent and synergizes with decabarzine for a greater antitumor effect. Formulations containing LY2090314 are under clinical investigation for the treatment of advanced solid tumors.{39185}